Auxin regulates endosperm cellularization in Arabidopsis.

The endosperm is an ephemeral tissue that nourishes the developing embryo, similar to the placenta in mammals. In most angiosperms, endosperm development starts as a syncytium, in which nuclear divisions are not followed by cytokinesis. The timing of endosperm cellularization largely varies between species, and the event triggering this transition remains unknown. Here we show that increased auxin biosynthesis in the endosperm prevents its cellularization, leading to seed arrest. Auxin-overproducing seeds phenocopy paternal-excess triploid seeds derived from hybridizations of diploid maternal plants with tetraploid fathers. Concurrently, auxin-related genes are strongly overexpressed in triploid seeds, correlating with increased auxin activity. Reducing auxin biosynthesis and signaling reestablishes endosperm cellularization in triploid seeds and restores their viability, highlighting a causal role of increased auxin in preventing endosperm cellularization. We propose that auxin determines the time of endosperm cellularization, and thereby uncovered a central role of auxin in establishing hybridization barriers in plants.

Endosperm cellularization failure induces a dehydration-stress response leading to embryo arrest.

The endosperm is a nutritive tissue supporting embryo growth in flowering plants. Most commonly, the endosperm initially develops as a coenocyte (multinucleate cell) and then cellularizes. This process of cellularization is frequently disrupted in hybrid seeds generated by crosses between different flowering plant species or plants that differ in ploidy, resulting in embryo arrest and seed lethality. The reason for embryo arrest upon cellularization failure remains unclear. In this study, we show that triploid Arabidopsis thaliana embryos surrounded by uncellularized endosperm mount an osmotic stress response that is connected to increased levels of abscisic acid (ABA) and enhanced ABA responses. Impairing ABA biosynthesis and signaling aggravated triploid seed abortion, while increasing endogenous ABA levels as well as the exogenous application of ABA-induced endosperm cellularization and suppressed embryo growth arrest. Taking these results together, we propose that endosperm cellularization is required to establish dehydration tolerance in the developing embryo, ensuring its survival during seed maturation.

Multiple wheat genomes reveal global variation in modern breeding.

Advances in genomics have expedited the improvement of several agriculturally important crops but similar efforts in wheat (Triticum spp.) have been more challenging. This is largely owing to the size and complexity of the wheat genome1, and the lack of genome-assembly data for multiple wheat lines2,3. Here we generated ten chromosome pseudomolecule and five scaffold assemblies of hexaploid wheat to explore the genomic diversity among wheat lines from global breeding programs. Comparative analysis revealed extensive structural rearrangements, introgressions from wild relatives and differences in gene content resulting from complex breeding histories aimed at improving adaptation to diverse environments, grain yield and quality, and resistance to stresses4,5. We provide examples outlining the utility of these genomes, including a detailed multi-genome-derived nucleotide-binding leucine-rich repeat protein repertoire involved in disease resistance and the characterization of Sm16, a gene associated with insect resistance. These genome assemblies will provide a basis for functional gene discovery and breeding to deliver the next generation of modern wheat cultivars.

Epigenetic and transcriptional consequences in the endosperm of chemically induced transposon mobilization in Arabidopsis.

Genomic imprinting, an epigenetic phenomenon leading to parent-of-origin-specific gene expression, has independently evolved in the endosperm of flowering plants and the placenta of mammals-tissues crucial for nurturing embryos. While transposable elements (TEs) frequently colocalize with imprinted genes and are implicated in imprinting establishment, direct investigations of the impact of de novo TE transposition on genomic imprinting remain scarce. In this study, we explored the effects of chemically induced transposition of the Copia element ONSEN on genomic imprinting in Arabidopsis thaliana. Through the combination of chemical TE mobilization and doubled haploid induction, we generated a line with 40 new ONSEN copies. Our findings reveal a preferential targeting of maternally expressed genes (MEGs) for transposition, aligning with the colocalization of H2A.Z and H3K27me3 in MEGs-both previously identified as promoters of ONSEN insertions. Additionally, we demonstrate that chemically-induced DNA hypomethylation induces global transcriptional deregulation in the endosperm, leading to the breakdown of MEG imprinting. This study provides insights into the consequences of chemically induced TE remobilization in the endosperm, revealing that chemically-induced epigenome changes can have long-term consequences on imprinted gene expression.

Ectopic application of the repressive histone modification H3K9me2 establishes post-zygotic reproductive isolation in Arabidopsis thaliana.

Hybrid seed lethality as a consequence of interspecies or interploidy hybridizations is a major mechanism of reproductive isolation in plants. This mechanism is manifested in the endosperm, a dosage-sensitive tissue supporting embryo growth. Deregulated expression of imprinted genes such as ADMETOS (ADM) underpin the interploidy hybridization barrier in Arabidopsis thaliana; however, the mechanisms of their action remained unknown. In this study, we show that ADM interacts with the AT hook domain protein AHL10 and the SET domain-containing SU(VAR)3-9 homolog SUVH9 and ectopically recruits the heterochromatic mark H3K9me2 to AT-rich transposable elements (TEs), causing deregulated expression of neighboring genes. Several hybrid incompatibility genes identified in Drosophila encode for dosage-sensitive heterochromatin-interacting proteins, which has led to the suggestion that hybrid incompatibilities evolve as a consequence of interspecies divergence of selfish DNA elements and their regulation. Our data show that imbalance of dosage-sensitive chromatin regulators underpins the barrier to interploidy hybridization in Arabidopsis, suggesting that reproductive isolation as a consequence of epigenetic regulation of TEs is a conserved feature in animals and plants.

New paradigms in the study of the cholinergic system and metabolic diseases: Acetyl-and-butyrylcholinesterase.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are enzymes that belong to the neuromuscular cholinergic system, their main function is to hydrolyze the neurotransmitter acetylcholine (ACh), through their hydrolysis these enzymes regulate the neuronal and neuromuscular cholinergic system. They have recently attracted considerable attention due to the discovery of new enzymatic and nonenzymatic functions. These discoveries have aroused the interest of numerous scientists, consolidating the relevance of this group of enzymes. Recent investigations have revealed a positive correlation between several risk factors for metabolic syndrome (MetS) and the expression of cholinesterases (ChE's), which underscore the impact of high ChE's activity on the pro-inflammatory state associated with MetS. In addition, the excessive hydrolysis of ACh and other choline esters (succinylcholine, propionylcholine, butyrylcholine, etc.) by both ChE's results in the overproduction of fatty acid precursor metabolites, which facilitate the synthesis of very low-density lipoproteins and triacylglycerols. Participation in these processes may represent the link between ChE's and metabolic disorders. However, further scientific research is required to fully elucidate the involvement of ChE's in metabolic diseases. This review aims to collect recent research studies that contribute to understanding the association between the cholinergic system and metabolic diseases.

Fully exploiting SNP arrays: a systematic review on the tools to extract underlying genomic structure.

Single nucleotide polymorphisms (SNPs) are the most abundant type of genomic variation and the most accessible to genotype in large cohorts. However, they individually explain a small proportion of phenotypic differences between individuals. Ancestry, collective SNP effects, structural variants, somatic mutations or even differences in historic recombination can potentially explain a high percentage of genomic divergence. These genetic differences can be infrequent or laborious to characterize; however, many of them leave distinctive marks on the SNPs across the genome allowing their study in large population samples. Consequently, several methods have been developed over the last decade to detect and analyze different genomic structures using SNP arrays, to complement genome-wide association studies and determine the contribution of these structures to explain the phenotypic differences between individuals. We present an up-to-date collection of available bioinformatics tools that can be used to extract relevant genomic information from SNP array data including population structure and ancestry; polygenic risk scores; identity-by-descent fragments; linkage disequilibrium; heritability and structural variants such as inversions, copy number variants, genetic mosaicisms and recombination histories. From a systematic review of recently published applications of the methods, we describe the main characteristics of R packages, command-line tools and desktop applications, both free and commercial, to help make the most of a large amount of publicly available SNP data.

Sex differences in the effectiveness and tolerability of dolutegravir plus rilpivirine as a switch strategy in people living with HIV.

INTRODUCTION: Dolutegravir + rilpivirine (DTG + RPV) is an effective antiretroviral therapy regimen approved in clinical guidelines as a switch therapy for virologically suppressed people with HIV. Our study aimed to compare the effectiveness and tolerability of DTG + RPV in women and men in real-world clinical practice. METHODS: This was a retrospective analysis of treatment-experienced people with HIV from a large HIV unit who switched to DTG + RPV. We analysed treatment effectiveness, rates of adverse events and discontinuation, and metabolic changes after 48 weeks of treatment. HIV-RNA levels <50 copies/mL were analysed at 48 weeks using both intention-to treat analysis (where missing data were interpreted as failures) and per-protocol analysis (excluding those with missing data or changes due to reasons other than virological failure). Outcomes were compared between women and men based on sex at birth. RESULTS: A total of 307 patients were selected (71 women and 236 men). No transgender people were included. At baseline, women had lived with HIV infection and received antiretroviral therapy for longer than men (23.2 vs 17.4 years and 18.9 vs 14.2 years, respectively). In the intention-to-treat analysis, 74.6% (95% confidence interval [CI] 63.4-83.3%) of women and 83.5% (95% CI 78.2-87.7) of men had HIV-RNA <50 copies/mL. In the per-protocol analysis, 96.4% (95% CI 87.7-99) of women and 99% (95% CI 98.9-99.7) of men had HIV-RNA levels <50 copies/mL. Two women and two men had HIV-RNA >50 copies/mL at 48 weeks. Discontinuation due to adverse events was more frequent in women than in men: 12.7% vs 7.2% (p < 0.02). Neuropsychiatric and gastrointestinal events were the most frequently reported. A median (interquartile range) weight gain of 1.9 kg (0-4.2) in women and 1.2 kg (-1-3.1) in men was reported (median of differences between baseline visit and week 48); the remaining changes in metabolic parameters were neutral. CONCLUSIONS: DTG + RPV exhibited good and similar virological effectiveness in women and men in real-world settings. However, poorer tolerability and more treatment interruptions were observed in women.

Congenital Zika virus infection impacts on male mouse offspring's reproductive biology.

In brief: Congenital ZIKV infection promotes alarming effects on male offspring's reproductive biology. This study showed the presence of the ZIKV antigen in the testis parenchyma, decreased testosterone levels, and sperm abnormalities in male offspring born to infected mothers. Abstract: Infection with ZIKV during pregnancy is associated with fetal developmental problems. Although neurological issues are being explored more in experimental studies, limited research has focused on the reproductive health consequences for offspring born to infected mothers. In this context, this study aimed to assess the impact of ZIKV infection during pregnancy on the testes and sperm of adult male offspring. Female mice were intraperitoneally inoculated with a Brazil strain of ZIKV during the 5.5th day of embryonic gestation. The offspring were evaluated 12 weeks after birth to analyze cellular and molecular changes in the testes and sperm. A novel approach combining variable-angle spectroscopic ellipsometry and machine learning modeling was also introduced for sperm sample analysis. The study revealed the presence of ZIKV protein in the testis parenchyma of adult male offspring born to infected mothers. It was shown that the testes exhibited altered steroidogenesis and inflammatory mediators, in addition to significant issues with spermiogenesis that resulted in sperm with DNA fragmentation, head defects, and protamination failure. Additionally, sperm dielectric properties and artificial intelligence showed potential for rapid identification and classification of sperm samples from infected mice. These findings provide crucial insights into the reproductive risks for men born from ZIKV-infected pregnant women.

Analyzing the role of ACE2, AR, MX1 and TMPRSS2 genetic markers for COVID-19 severity.

BACKGROUND: The use of molecular biomarkers for COVID-19 remains unconclusive. The application of a molecular biomarker in combination with clinical ones that could help classifying aggressive patients in first steps of the disease could help clinician and sanitary system a better management of the disease. Here we characterize the role of ACE2, AR, MX1, ERG, ETV5 and TMPRSS2 for trying a better classification of COVID-19 through knowledge of the disease mechanisms. METHODS: A total of 329 blood samples were genotyped in ACE2, MX1 and TMPRSS2. RNA analyses were also performed from 258 available samples using quantitative polymerase chain reaction for genes: ERG, ETV5, AR, MX1, ACE2, and TMPRSS2. Moreover, in silico analysis variant effect predictor, ClinVar, IPA, DAVID, GTEx, STRING and miRDB database was also performed. Clinical and demographic data were recruited from all participants following WHO classification criteria. RESULTS: We confirm the use of ferritin (p < 0.001), D-dimer (p < 0.010), CRP (p < 0.001) and LDH (p < 0.001) as markers for distinguishing mild and severe cohorts. Expression studies showed that MX1 and AR are significantly higher expressed in mild vs severe patients (p < 0.05). ACE2 and TMPRSS2 are involved in the same molecular process of membrane fusion (p = 4.4 × 10-3), acting as proteases (p = 0.047). CONCLUSIONS: In addition to the key role of TMPSRSS2, we reported for the first time that higher expression levels of AR are related with a decreased risk of severe COVID-19 disease in females. Moreover, functional analysis demonstrates that ACE2, MX1 and TMPRSS2 are relevant markers in this disease.

Global cross-sectional survey on neonatal pharmacologic sedation and analgesia practices and pain assessment tools: impact of the sociodemographic index (SDI).

BACKGROUND: There is variability in the use of sedatives and analgesics in neonatal intensive care units (NICUs). We aimed to investigate the use of analgesics and sedatives and the management of neonatal pain and distress. METHODS: This was a global, prospective, cross-sectional study. A survey was distributed May-November 2022. The primary outcome of this research was to compare results between countries depending on their socio-sanitary level using the sociodemographic index (SDI). We organized results based on geographical location. RESULTS: The survey collected 1304 responses, but we analyzed 924 responses after database cleaning. Responses from 98 different countries were analyzed. More than 60% of NICUs reported having an analgosedation guideline, and one-third of respondents used neonatal pain scales in more than 80% of neonates. We found differences in the management of sedation and analgesia between NICUs on different continents, but especially between countries with different SDIs. Countries with a higher SDI had greater availability of and adherence to analgosedation guidelines, as well as higher rates of analgosedation for painful or distressing procedures. Countries with different SDIs reported differences in analgosedation for neonatal intubation, invasive ventilation, and therapeutic hypothermia, among others. CONCLUSIONS: Socio-economic status of countries impacts on neonatal analgosedation management. IMPACT: There is significant variability in the pain management practices in neonates. There is a lack of knowledge related to how neonatal pain management practices differ between regions. Sociodemographic index is a key factor associated with differences in neonatal pain management practices across global regions.

Tumor growth for remodeling process: A 2D approach.

This paper aims to present a comprehensive framework for coupling tumor-bone remodeling processes in a 2-dimensional geometry. This is achieved by introducing a bio-inspired damage that represents the growing tumor, which subsequently affects the main populations involved in the remodeling process, namely, osteoclasts, osteoblasts, and bone tissue. The model is constructed using a set of differential equations based on the Komarova's and Ayati's models, modified to incorporate the bio-inspired damage that may result in tumor mass formation. Three distinct models were developed. The first two models are based on the Komarova's governing equations, with one demonstrating an osteolytic behavior and the second one an osteoblastic model. The third model is a variation of Ayati's model, where the bio-inspired damage is induced through the paracrine and autocrine parameters, exhibiting an osteolytic behavior. The obtained results are consistent with existing literature, leading us to believe that our in-silico experiments will serve as a cornerstone for paving the way towards targeted interventions and personalized treatment strategies, ultimately improving the quality of life for those affected by these conditions.

Comparison of the SLE Risk Probability Index (SLERPI) scale against the European League Against Rheumatism/American College of Rheumatology (ACR/EULAR) and Systemic Lupus International Collaborating Clinics (SLICC) criteria.

INTRODUCTION: Timely diagnosis and proper recognition of Systemic Lupus Erythematosus (SLE) is essential to establish early management in inpatients and outpatients. There are different classification scales to identify SLE, which include various clinical and serological aspects. In 2021, the SLE Risk Probability Index (SLERPI) was published, which focuses predominantly on the clinical characteristics of patients with suspected SLE and uses a simple algorithm for early recognition of the disease. The aim of this study is to compare the European League Against Rheumatism/American College of Rheumatology (ACR/EULAR) classification criteria, the Systemic Lupus International Collaborating Clinics (SLICC) criteria, and the SLERPI criteria in a cohort of Colombian patients with SLE and to analyze the correlations observed between their absolute scores. METHODS: A registry of SLE patients from two referral hospitals in Bogotá, Colombia, was used. 2021 SLERPI, 2019 ACR/EULAR, and 2012 SLICC scores were calculated for each patient and the correlations found between the scales were analyzed. The sensitivities of each were compared, and frequency analyses were conducted among different clinical and laboratory variables. RESULTS: Between 2016 and 2019, 146 patients diagnosed with SLE were registered, including inpatients and outpatients. The median age was 36 years (interquartile range 26-51), and 82.2% were women. According to the SLERPI criteria, a high prevalence of antinuclear antibodies (92%), immunological disorders (71%), and arthritis (64%) were observed. The most used treatments were corticosteroids (87.6%) and chloroquine (67.8%). A Spearman evaluation analysis was performed, with a moderately strong correlation of 0.76 (p = .000) between the SLERPI and ACR/EULAR scales and very strong correlation of 0.80 (p = .000) between the SLERPI and SLICC. Patients classified with SLE according to the SLERPI scale exhibited a higher incidence of hematological compromise, along with elevated levels of serological markers such as anti-DNA antibodies. Additionally, this group more commonly received treatments involving corticosteroids and azathioprine, and displayed a higher prevalence of hypertension. CONCLUSION: The SLERPI scale could be useful in the diagnosis of SLE, especially in early stages, given its good correlation with other classification scales and its good sensitivity.

Perspectives of primary care physicians in Spain on malaria: a cross-sectional survey and retrospective review of cases.

BACKGROUND: In Spain, the risk of imported malaria has increased in recent years due to the rise in international travel and migration. Little is known about the knowledge, information sources, clinical practice, and specific needs of primary care physicians (PCPs) concerning malaria despite the pivotal role played by these professionals in managing the health of tourists. The objective of this study was to assess the knowledge, attitudes, and practices of PCPs in Spain regarding malaria. METHODS: This research analyses data from (1) a cross-sectional nationwide survey assessing the knowledge and attitudes of PCPs regarding malaria, and (2) a retrospective review of 373 malaria cases appearing in primary care medical records (PCMRs) in the Madrid area over the past 15 years to determine how cases were documented, managed, or characterized in the primary care setting. RESULTS: The survey findings reveal a modest level of self-perceived familiarity with malaria (221/360, 57.6%), even though 32.8% of the practitioners reported having delivered care for confirmed or suspected cases of the disease, these practitioners had greater knowledge of malaria (80.4%) compared to physicians who reported not having delivered care for malaria (19.6%, p < 0.001). Ten percent of the survey participants did not know the name of the mosquito that transmits malaria, and only 40.7% would promptly request malaria testing for a traveller with symptoms after a trip to an endemic area. Responses provided by younger PCPs varied to a greater extent than those of their more experienced colleagues regarding prevention practices and patient management. A review of PCMRs showed that only 65% of all patients were recorded as such. Among those registered, only 40.3% had a documented malaria episode, and of those, only 16.6% received proper follow-up. Only 23.7% of the patients with a PCMR had a record that specifically indicated travel to an endemic country or travel classified as visiting friends and relatives (VFR). CONCLUSIONS: The findings of this study underscore the critical role of PCPs in the field of travel medicine, particularly given the increase in imported malaria cases. These results highlight the need for targeted training in travel medicine and the need to ensure optimal patient education in care settings.

A case study on pharmaceutical residues and antimicrobial resistance genes in Costa Rican rivers: A possible route of contamination for feline and other species.

In this investigation, the presence of antibiotics and pharmaceuticals in Costa Rican surface waters, specifically in regions near feline habitats, was examined. The study revealed that 47% of the water samples contained detectable traces of at least one antibiotic. Ciprofloxacin and norfloxacin were the most frequently detected compounds, each with a detection rate of 27%. Other antibiotics, such as erythromycin, roxithromycin, and trimethoprim, were also found but at lower frequencies, around 14%. Notably, all antibiotic concentrations remained below 10 ng/L, with ciprofloxacin, norfloxacin, and erythromycin showing the highest concentrations. Furthermore, the investigation revealed the presence of non-antibiotic pharmaceutical residues in the water samples, typically at concentrations below 64 ng/L. Tramadol was the most frequently detected compound, present in 18% of the samples. The highest concentrations were observed for acetaminophen and tramadol, measuring 64 and 10 ng/L, respectively. Comparing these findings with studies conducted in treated wastewater and urban rivers, it became evident that the concentrations of antibiotics and pharmaceuticals were notably lower in this study. While previous research reported higher values, the limited number of studies conducted in protected areas raises concerns about the potential environmental impact on biodiversity. In summary, these results emphasize the importance of monitoring pharmaceutical residues and antimicrobial resistance genes ARGs in vulnerable ecosystems, especially those in close proximity to feline habitats in Costa Rica. Additionally, the study delved into the detection of (ARGs). All tested water samples were positive for at least one ARG, with the blaTEM gene being the most prevalent at 82%, followed by tetS at 64% and qnrB at 23%. Moreover, this research shed light on the complexity of evaluating ARGs in environmental samples, as their presence does not necessarily indicate their expression. It also highlighted the potential for co-selection and co-regulation of ARGs, showcasing the intricate behaviors of these genes in aquatic environments.

Early results of eTEP access surgery with preperitoneal repair of primary midline ventral hernias and diastasis recti. A 33 patient case series of "PeTEP".

BACKGROUND: This article aims to share the initial experience of the preperitoneal eTEP approach and its potential benefits in a selected group of patients. The eTEP Rives-Stoppa is a proven minimally invasive surgical technique for the treatment of ventral midline and off-midline hernias that has shown to be a solid, durable, and reproducible repair. The preperitoneal eTEP repair is a surgical technique that brings together the extraperitoneal access surgery with a preperitoneal repair for primary midline hernias avoiding posterior rectus sheath division and preservation of the retrorectus space while being able to treat simultaneous diastasis recti. METHODS: The analysis included 33 patients operated with the preperitoneal eTEP approach from September 2022 to September 2023 in patients with primary small to medium (< 4 cm) midline hernias, single or multiple defects with or without diastasis recti. Age, gender, hernia characteristics, operative time, and surgical site occurrences will be discussed, as well as fine details and landmarks in the operative technique. RESULTS: 33 consecutive patients were operated, 19 female (57.5%) and 14 males (42.5%) between 32 and 63 years of age, the most common comorbidity found was obesity (BMI > 30). In 70% of the cases, operative time was 90 min ± 25 min. The average hospital stay was one day, while 12 went home the same day, and so far, no reoccurrences have been reported. CONCLUSIONS: We believe the preperitoneal eTEP approach for small to medium primary midline hernias is an effective and solid repair that combines excellent features of proven surgical techniques and eliminates the need for posterior rectus sheath division while saving the retrorectus space, among other benefits that will be discussed. The reproducibility of the technique remains to be proven.

Mass Spectrometry Identification of Biomarkers in Extracellular Vesicles From Plasmodium vivax Liver Hypnozoite Infections.

Latent liver stages termed hypnozoites cause relapsing Plasmodium vivax malaria infection and represent a major obstacle in the goal of malaria elimination. Hypnozoites are clinically undetectable, and presently, there are no biomarkers of this persistent parasite reservoir in the human liver. Here, we have identified parasite and human proteins associated with extracellular vesicles (EVs) secreted from in vivo infections exclusively containing hypnozoites. We used P. vivax-infected human liver-chimeric (huHEP) FRG KO mice treated with the schizonticidal experimental drug MMV048 as hypnozoite infection model. Immunofluorescence-based quantification of P. vivax liver forms showed that MMV048 removed schizonts from chimeric mice livers. Proteomic analysis of EVs derived from FRG huHEP mice showed that human EV cargo from infected FRG huHEP mice contain inflammation markers associated with active schizont replication and identified 66 P. vivax proteins. To identify hypnozoite-specific proteins associated with EVs, we mined the proteome data from MMV048-treated mice and performed an analysis involving intragroup and intergroup comparisons across all experimental conditions followed by a peptide compatibility analysis with predicted spectra to warrant robust identification. Only one protein fulfilled this stringent top-down selection, a putative filamin domain-containing protein. This study sets the stage to unveil biological features of human liver infections and identify biomarkers of hypnozoite infection associated with EVs.

A network analysis of Hurricane Maria-related traumatic stress and substance use among Puerto Rican youth.

Youth exposed to natural disasters are at risk of developing trauma-related symptoms as well as engaging in substance use. Although previous research has established associations between disaster-related stressors and substance use in youth, less has focused on how symptoms of posttraumatic stress disorder (PTSD) may underpin this association. The current study used network analysis to identify specific PTSD symptoms associated with substance use following a natural disaster. Participants were 91,732 youths (Grades 3-12) from across Puerto Rico who completed a needs assessment 5-9 months after Hurricane Maria made landfall in September 2017. We examined associations between PTSD symptoms and substance use, identified clusters of symptoms and bridges between them, and explored age- and binary gender-related differences in associations between specific PTSD symptoms and substance use. Analyses identified two symptom communities: (a) arousal and reactivity, negative alterations in cognition and mood, and substance use, and (b) avoidance and intrusion. Broader findings suggested that substance use was most strongly associated with PTSD-related irritability and angry outbursts among youths. Surrounding nodes explained only 4.1% of the variance in substance use, but this was higher among youths who reported not having a supportive adult, R2 = 8.5; friend, R2 = 7.9; or teacher/counselor, R2 = 7.7, in their life. The bridge symptoms of sleep disruption and physiological reactivity were identified as potentially critical intervention targets for disrupting PTSD symptom networks after a natural disaster. Implications for triaged mental health care following natural disasters and directions for future research are discussed.

Role of dexamethasone in controlling the proinflammatory cytokine cascade in the first episode of paediatric acute pyelonephritis.

AIM: Febrile urinary tract infection is a common bacterial infection in childhood. The kidney damage after acute pyelonephritis (APN) could be related to the stimulation of the proinflammatory response. We aimed to investigate the role of inflammatory cytokines and the effect of dexamethasone after a first episode of APN. METHODS: Subanalysis of the DEXCAR RCT in which children with confirmed APN (1 month-14 years) were randomly assigned to receive a 3 days course of either intravenous dexamethasone or placebo. Urinary cytokine levels at diagnosis and after 72 h of treatment were measured. RESULTS: Ninety-two patients were recruited. Younger patients, males and those with abnormalities in the ultrasound study or vesicoureteral reflux showed higher values of urinary cytokines. Patients with severe APN had higher Tumour Necrosis Factor (TNF)α levels (81.0 ± 75.8 vs. 33.6 ± 48.5 pg/mg creatinine, p = 0.015). Both intervention groups showed similar basal clinical characteristics, including urinary cytokine levels. Treatment reduced urinary cytokine levels irrespective of dexamethasone administration. Neither the intervention group nor the urinary cytokine levels modulated the development of kidney scars. CONCLUSION: Basal urinary cytokines were associated with age, abnormal ultrasound and vesicoureteral reflux. Patients with severe APN had higher TNFa urinary levels. Administration of dexamethasone in children with APN does not improve the control of the proinflammatory cytokine cascade.

Hybrid seed incompatibility in Capsella is connected to chromatin condensation defects in the endosperm.

Hybridization of closely related plant species is frequently connected to endosperm arrest and seed failure, for reasons that remain to be identified. In this study, we investigated the molecular events accompanying seed failure in hybrids of the closely related species pair Capsella rubella and C. grandiflora. Mapping of QTL for the underlying cause of hybrid incompatibility in Capsella identified three QTL that were close to pericentromeric regions. We investigated whether there are specific changes in heterochromatin associated with interspecific hybridizations and found a strong reduction of chromatin condensation in the endosperm, connected with a strong loss of CHG and CHH methylation and random loss of a single chromosome. Consistent with reduced DNA methylation in the hybrid endosperm, we found a disproportionate deregulation of genes located close to pericentromeric regions, suggesting that reduced DNA methylation allows access of transcription factors to targets located in heterochromatic regions. Since the identified QTL were also associated with pericentromeric regions, we propose that relaxation of heterochromatin in response to interspecies hybridization exposes and activates loci leading to hybrid seed failure.